Search PubMed⌕ Search

Biomedical subjects

C Sureau

Publications and source records attributed to C Sureau.

At least 37 records · Page 2Linked to original sources

Interaction between hepatitis delta virus-encoded proteins and hepatitis B virus envelope protein domains.

Hepatitis delta virus (HDV) packaging requires prenylation of the HDV large protein (p27), as well as a direct protein-protein interaction between HDV proteins and hepatitis B virus (HBV) envelope protein domains. To investigate this interaction, we have analysed the binding capacity of baculovirus-expressed delta p24 and p27 proteins to synthetic peptides specific for the HBV envelope. Although a higher degree of binding was observed with p27, both p24 and p27 could bind HBV envelope peptides. One such peptide corresponded to residues 56-80 located in the cytosolic loop of the small HBV envelope protein, and another corresponded to 23 carboxy-terminal residues of the pre-S1 specific to the large HBV envelope protein. This indicates that in addition to p27, p24 may contribute to packaging of HDV through a protein-protein interaction with HBV envelope domains, and that an interaction between the pre-S1 polypeptide and delta proteins may play a role in infectivity.

Amino Acid Sequence↗

Historical perspectives: forgotten past, unpredictable future.

Intrapartum surveillance has in recent years become a matter of debate. Following its earlier development, first in auscultation and then 40 years ago in electronic monitoring, obstetricians accepted its use with great, perhaps too great, enthusiasm. Years later, attempts to evaluate the actual consequences of this use led to disappointment: although its benefit on perinatal mortality is acknowledged, two observations lead one to reconsider the legitimacy of its use. First the apparent lack of beneficial influence on neonatal long-term morbidity, and second the definite increase in the rate of caesarean section. Furthermore, recent comparative studies, despite some discrepancies, seem to indicate that clinical monitoring by auscultation leads to results as good as those from electronical monitoring, particularly with respect to fetal mortality and infant morbidity. These observations obviously merit careful consideration; some explanations may be put forward to explain these apparently surprising results. From a practical point of view, this discussion leads to two opposite choices for obstetric policy: either to 'go back' to auscultation or to try to identify indicators more specific to fetal asphyxia and increased risk of cerebral palsy, leading to more precise and fewer indications for caesarean section. This chapter on historical perspectives may be useful in pointing out what were the goals of the obstetric pioneers involved in electronic monitoring: definitely not to build theoretical considerations on the pathophysiology of fetal distress, but to gather continuous information about the fetal heart rate in the hope of detecting changes announcing fetal asphyxia before it becomes irremediable, and hence preventing fetal death. These promises have been fulfilled. It follows that continuous clinical monitoring, which provides the same kind of information, is quite likely to lead to similar clinical results. It also follows that this relatively cumbersome method has really nothing to do with the 'classical' clinical surveillance in use before the widespread acceptance of electronical monitoring. It may be beneficial to experiment with this specific type of clinical surveillance; it would be dangerous, however, to 'go back' to the type of monitoring practised 40 years ago.

Auscultation↗

Spectral analysis of fetal heart rate in flat recordings.

Flat heart rate recordings may be observed in different fetal states such as chronic distress and sleep. Their visual analysis do not allow the distinction between these two states. We used spectral analysis to study the heart rate patterns in 25 fetuses. Two significant (P < 5 x 10(-5)) groups were apparent from the determination of the position of the maximum energy peak (PMEP) in the high-frequency band (0.20-0.50 Hz): a PMEP at about 0.20 Hz (group 1), and another around 0.30 Hz (group 2). The two groups did not differ in spectral density (SD). The outcome of neonates showed that group 1 fetuses made good progress and produced healthy neonates; whereas group 2 comprised cases of chronic fetal distress, or even death in utero, and neonatal distress. The significance of this difference in PMEP between fetal heart rate patterns in chronic distress and sleep is unclear. Studies combining the assessment of fetal movements and the determination of PMEP are planned.

Female↗

Medical deresponsibilization.

The medical profession is facing a serious challenge. The increase of technology, risks, and costs of modern medicine leads to the intervention of third parties within the medical decision-making process. This is particularly true in reproductive medicine, where a large part of medical activities are not curative, not linked with actual abnormalities, but preventive, and frequently oriented more to desire and convenience than to needs. These third parties belong to the fields of economics, administration, law, public opinion, mediatic power. This trend is universal, with some specific characteristics varying by country. The increased risk of litigation leads to an increase of all aspects of defensive medicine, with obvious medical, practical, economic deleterious consequences.

Delivery of Health Care↗

Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR.

To further explore the controversial potential for extrahepatic replication of hepatitis C virus (HCV), the highly strand-specific rTth method of reverse transcriptase PCR was used to examine sera, liver, peripheral blood mononuclear cells, and other extrahepatic tissues from HCV-infected chimpanzees and humans. Positive-strand HCV RNA was present in the liver at approximately 10-fold-higher levels than negative-strand HCV RNA. No negative-strand RNA was detected in peripheral blood mononuclear cells or other extrahepatic tissues despite the presence of abundant positive-strand RNA. These data demonstrate that within the limits of sensitivity of this highly strand-specific reverse transcriptase PCR method, no extrahepatic replication of HCV was detected.

Animals↗

Demonstration of in vitro infection of chimpanzee hepatocytes with hepatitis C virus using strand-specific RT/PCR.

Analysis of hepatitis C virus (HCV) replication has been hampered due to the difficulty encountered in in vitro cultivation of the virus in conventional tissue culture systems. In this study, primary chimpanzee hepatocyte cultures maintained in a serum-free medium formulation were susceptible to in vitro infection with HCV. In order to document infection, two new methods of reverse transcription/polymerase chain reaction were developed that permit accurate distinction between positive and negative strand HCV RNA. One method relied upon the use of a tagged cDNA primer, while the second method employed a thermostable reverse transcriptase. Following inoculation of chimpanzee hepatocytes with HCV, intracellular positive and negative strand HCV RNA were detectable 4 days postinfection and throughout the remainder of the experimental period, 25 days. Analysis of HCV-inoculated baboon hepatocytes revealed a total absence of negative strand HCV RNA, while residual positive strand RNA from the inoculum could be detected for up to 11 days. The in vitro replication of HCV RNA in chimpanzee hepatocytes could be suppressed by alpha-interferon. This system should be amenable to the study of HCV replication, antiviral compounds, and the development of neutralization assays.

Animals↗

Quantification of the fetal heart rate variability by spectral analysis of fetal well-being and fetal distress.

Our objectives were to increase the discrimination between fetal distress and fetal well-being, using fetal heart rate spectral analysis. Monitoring of the heart rate from 259 fetuses was done between 26 and 42 weeks, interpreted with classical criteria, and analysed with the spectral analysis method we developed. The fetal heart rate spectrum analysis performed on these recordings allow discrimination of fetal distress from the normal state using the energy value and frequency of the maximal energy in the high frequency band. We can conclude that the spectral analysis produces two significant parameters which could contribute to a multivariate approach to assessments of the physiological mechanisms of heart rate variability.

Female↗

The middle hepatitis B virus envelope protein is not necessary for infectivity of hepatitis delta virus.

The hepatitis delta virus (HDV) envelope contains the large (L), middle (M), and small (S) surface proteins encoded by coinfecting hepatitis B virus. Although HDV-like particles can be assembled with only the S protein in the envelope, the L protein is essential for infectivity in vitro (C. Sureau, B. Guerra, and R. Lanford, J. Virol. 67:366-372, 1993). Here, we demonstrate that the M protein, previously described as carrying a site for binding to polymerized human albumin, is not necessary for infectivity. HDV-like particles coated with the S plus L or the S plus M plus L proteins are infectious in primary cultures of chimpanzee hepatocytes. We conclude that the S and L proteins serve two essential functions in the HDV replication cycle; the S protein ensures the export of the HDV genome from an infected cell by forming a particle, and the L protein ensures its import into a human hepatocyte.

Animals↗

[Morals, logic and ethics in reproductive medicine].

Human reproduction has always been a matter of philosophical interrogations and controversies. This situation has been reinforced by the technical evolution which has occurred during the past years. Both hopes and concerns have been raised at the same time. Two recent advancements deserve consideration and are given as demonstrative examples: intracytoplasmic injection of spermatozoon, preimplantatory diagnosis. Their consequences are very important for both the medical and the philosophical approach. One of the questions which arises at this occasion is to determine if research on pre embryos is legitimate or not. This evolution has provoked some reluctancy and several criticisms concerning the future of the children obtained by such techniques: the risk of slippery slope, possibly leading to a form of eugenics, and the fundamental and philosophical problem of the status of the embryo. However, behind these discussions a deeper and heavier controversial matter may be discovered; it deals with the role and the responsibilities of the governmental power. An opposition does exist between two different perceptions: on the one hand, the concept of a powerful governmental body, responsible for the respect of a statutory law, grounded on a sort of universal ethical rule, to be followed by all, a concept which bears the risk of totalitarianism; on the other hand, the concept of a law with a limited responsibility to protect public order, allowing a normal social life. Amongst the numerous responsibilities of the governmental power, one is often neglected, everywhere; its concerns the protection of the female life and health. Some examples are given. However the most frightening risk, much more dangerous than the frequently alleged risk of biological eugenics, is what can be called "economical eugenics". Again some examples are given, in all the systems of social protection. Submitted to ethical rules imposed by political and legal powers, and to the influence of economical forces, what will be the role and the responsibilities of the practitioner? Unfortunately the answer may be obvious: the only way is leading to a relinquishment of medical responsibility. Far away from the dialogue which was the rule of the "dual relationship" between the patient and the practitioner, away too from the more complicated situation of today, characterized by the intervention of "third parties", the evolution, probably unavoidable, appears to be towards the withdrawal of the psychological, moral, human and humanistic involvement of the practitioner, leading him or her to a technical role.(ABSTRACT TRUNCATED AT 400 WORDS)

Ethics, Medical↗

In vitro culture systems for hepatitis B and delta viruses.

The development of tissue culture technology has led to invaluable information in many fields of modern virology. Until recently, the lack of an in vitro culture system for the hepatitis B virus (HBV) was a considerable impediment to the study of its life cycle at the cellular and molecular levels. However, it did not prevent its isolation and molecular cloning. Such has been the case also for the hepatitis delta virus (HDV), the genome of which was cloned and sequenced before its replication could be observed in cultured cells. In recent years, tissue culture systems for HBV and HDV have been developed progressively by the identification of permissive, established cell lines for production of virions and susceptible primary hepatocyte cultures for infection assays. I will briefly review here the recent experiments that have contributed to replicate HBV and HDV in cell culture systems.

Animals↗

Role of the large hepatitis B virus envelope protein in infectivity of the hepatitis delta virion.

The hepatitis delta virus (HDV) is coated with large (L), middle (M), and small (S) envelope proteins encoded by coinfecting hepatitis B virus (HBV). To study the role of the HBV envelope proteins in the assembly and infectivity of HDV, we produced three types of recombinant particles in Huh7 cells by transfection with HBV DNA and HDV cDNA: (i) particles with an envelope containing the S HBV envelope protein only, (ii) particles with an envelope containing S and M proteins, and (iii) particles with an envelope containing S, M, and L proteins. Although the resulting S-, SM-, and SML-HDV particles contained both hepatitis delta antigen and HDV RNA, only particles coated with all three envelope proteins (SML) showed evidence of infectivity in an in vitro culture system susceptible to HDV infection. We concluded that the L HBV envelope protein, and more specifically the pre-S1 domain, is important for infectivity of HDV particles and that the M protein, which has been reported to bear a site for binding to polymerized albumin in the pre-S2 domain, is not sufficient for infectivity. Our data also show that the helper HBV is not required for initiation of HDV infection. The mechanism by which the L protein may affect HDV infectivity is discussed herein.

Animals↗